4-[1-(4-fluorophenyl)-2-methyl-1H-imidazol-4-ylethynyl]-2-methyl-pyridine | 761426-66-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[1-(4-fluorophenyl)-2-methyl-1H-imidazol-4-ylethynyl]-2-methyl-pyridine
• 英文别名: 4-[1-(4-Fluoro-phenyl)-2-methyl-1H-imidazol-4-ylethynyl]-2-methyl-pyridine；4-[2-[1-(4-fluorophenyl)-2-methylimidazol-4-yl]ethynyl]-2-methylpyridine
• CAS: 761426-66-8
• 化学式: C₁₈H₁₄FN₃
• 分子量: 291.328
• InChiKey: SAXJBNCVBXKLBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[1-(4-fluorophenyl)-2-methyl-1H-imidazol-4-ylethynyl]-2-methyl-pyridine 、 N,N-二甲基甲酰胺 生成 3-(4-fluoro-phenyl)-2-methyl-5-(2-methyl-pyridin-4-ylethynyl)-3H-imidazole-4-carbaldehyde
  参考文献：
  名称：

  Imidazole derivatives

  摘要：

  本发明提供4-[1-芳基咪唑-4-基乙炔基]-2-烷基吡啶和1-杂环芳基咪唑-4-基乙炔基]-2-烷基吡啶衍生物及其药学上可接受的盐，用于治疗或预防由代谢型谷氨酸受体5完全或部分介导的疾病。这些疾病包括，例如神经系统的急性、创伤性和慢性退行性过程，如阿尔茨海默病、老年性痴呆症、帕金森病、亨廷顿舞蹈症、肌萎缩性侧索硬化和多发性硬化症，精神疾病，如精神分裂症和焦虑、抑郁、疼痛和药物依赖症。

  公开号：

  US07153874B2
• 作为产物：
  描述：

  4-氟苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四丁基氟化铵 、 氧气 、 copper diacetate 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 4-[1-(4-fluorophenyl)-2-methyl-1H-imidazol-4-ylethynyl]-2-methyl-pyridine
  参考文献：
  名称：

  Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators: Discovery of 2-Chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (Basimglurant, RO4917523), a Promising Novel Medicine for Psychiatric Diseases

  摘要：

  Negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGlu5) have potential for the treatment of psychiatric diseases including depression, fragile X syndrome (FXS), anxiety, obsessive-compulsive disorders, and levodopa induced dyskinesia in Parkinson's disease. Herein we report the optimization of a weakly active screening hit 1 to the potent and selective compounds chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, 2) and 2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP, 3). Compound 2 is active in a broad range of anxiety tests reaching the same efficacy but at a 10- to 100-fold lower dose compared to diazepam and is characterized by favorable DMPK properties in rat and monkey as well as an excellent preclinical safety profile and is currently in phase II clinical studies for the treatment of depression and fragile X syndrome. Analogue 3 is the first reported mGlu5 NAM with a long half-life in rodents and is therefore an ideal tool compound for chronic studies in mice and rats.

  DOI：

  10.1021/jm501642c

文献信息

• [EN] IMIDAZOL-4-YL-ETHYNYL-PYRIDINE DERIVATIVES<br/>[FR] DERIVES DE L'IMIDAZOL-4-YL-ETHYNYL-PYRIDINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004080998A1

  公开（公告）日：2004-09-23

  4-[1-Aryl-imidazol-4-ylethynyl]-2-alkyl-pyridine and 1-heteroaryl-imidazol-4-ylethynyl]-2-alkyl-pyridine derivatives and pharmaceutically acceptable salts thereof for the treatment or prevention of disorders mediated full or in part by metabotropic glutamate receptor 5, e.g. acute, traumatic and chronic degenerative processes of the nervous system, such as Alzheimer's disease, senile dementia, Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis and multiple sclerosis, psychiatric diseases such as schizophrenia and anxiety, depression, pain and drug dependency.

  4-[1-芳基-咪唑-4-基乙炔基]-2-烷基吡啶和1-杂环芳基-咪唑-4-基乙炔基]-2-烷基吡啶衍生物及其药用可接受盐，用于治疗或预防由代谢型谷氨酸受体5完全或部分介导的疾病，例如神经系统的急性、创伤性和慢性退行性过程，如阿尔茨海默病、老年性痴呆、帕金森病、亨廷顿舞蹈症、肌萎缩侧索硬化和多发性硬化，精神疾病如精神分裂症和焦虑、抑郁、疼痛和药物依赖。
• IMIDAZOL-4-YL-ETHYNYL-PYRIDINE DERIVATIVES
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1606277B1

  公开（公告）日：2008-05-14
• EP1606277B8
  申请人：——

  公开号：EP1606277B8

  公开（公告）日：2008-10-15
• PROCESS FOR CONVERTING DIFFICULTLY CONVERTIBLE OXYGENATES TO GASOLINE
  申请人：Haldor Topsoe A/S

  公开号：EP1920029A1

  公开（公告）日：2008-05-14
• DEGRADABLE POLYMERS AND MONOMERS THEREFOR
  申请人：The Board of Trustees of the University of Illinois

  公开号：US20210317058A1

  公开（公告）日：2021-10-14

  Hydroxyacetal or hydroxyketal monomers, processes for their preparation, their use to produce degradable polymers, hydroxy-functional intermediates resulting from degradation, and repurposed polymers made from the hydroxy-functional intermediates are described. The invention avoids the energy-intensive conditions normally used to degrade polyurethanes and generates new hydroxy-functional intermediates that can be repurposed or upcycled. Polyurethanes and melamines, materials once destined for a landfill, can have a second life. Incorporation of a photoacid generator into microcapsule core materials and fabrication of the shell from the hydroxy-functional acetal or ketal monomers promotes facile, inside-out, solid-state degradation of the microcapsule shell triggered by UV light and acid generation in a hydrophobic environment. This enables controlled release of flavors, fragrances, biocides, agricultural actives, or other oil-based beneficial agents from within the microcapsules.